The proposed research is based on our previous observations that collagen, proteoglycan, and DNA synthesis are greatly stimulated when rabbit articular cartilage is placed in long term organ culture. The collagen phenotype is relatively stable in organ culture but in serial monolayer culture type II synthesis is terminated. We will study the regulation of collagen and proteoglycan synthesis by somatomedins and related growth factors using articular chondrocytes. This work will focus on changes in chondrocyte sensitivity to somatomedin with age and pathology. Fluctuations in the number and affinity of membrane receptors will be evaluated. Both biosynthetic and immunohistological collagen typing will be used to extend our knowledge of environmental influences on chondrocyte phenotypic changes. Emphasis will be palced on cell attachment, matrix deposition, proliferation, lysosomal enzymes, and hyaluronic acid. Proteoglycan deposition will be studied in an in vitro system where the rate of deposition and synthesis can be independently varied. This will permit the relative importance of proteoglycan aggregation and matrix binding to be determined. The significance of the data to osteoarthritis will be confirmed by parallel studies using human and bovine osteoarthritic and normal cartilage.